Fixed Dose Flavonoid Isoquercetin on Thrombo-Inflammatory Biomarkers in Subjects With Stable Sickle Cell Disease
- Registration Number
- NCT04514510
- Brief Summary
Background:
Sickle cell disease (SCD) is an inherited hemoglobin disorder. People with SCD have an increased chance for getting blood clots. Researchers want to see if a dietary supplement called isoquercetin can decrease levels of inflammation and blood clotting in people with SCD.
Objective:
To see how isoquercetin works in people with SCD.
Eligibility:
Adults age 18-70 years old who have SCD and are in a steady-state (have not experienced a pain crisis in the last 60 days and, if taking hydroxyurea, have not had a dose change in the past 90 days).
Design:
Participants will be screened with a physical exam, medical history, medicine review, and blood tests.
Participants will be put in 1 of 2 treatment groups. They will take 4 capsules of isoquercetin or placebo all at once, by mouth, every day for 4 weeks. They will get a pill dispenser and keep a medicine diary.
Participants may have an optional near infrared spectroscopy (NIRS) test to measure how treatment affects blood flow. In this test, probes will be placed on the skin to measure tissue oxygen level and blood flow. A blood pressure cuff placed on the arm will be filled with air briefly to restrict the blood flow in the arm (for up to 5 minutes) and then released. Participants may also be asked to breathe at a certain rate or hold their breath for as long as they can during measurements.
Participants will take folic acid once a day.
Participants will have an end-of-study drug visit. They will discuss any side effects and repeat some of the screening tests. They may have an additional optional NIRS test.
About a month after the end of study drug visit, participants will be contacted by phone to see if they have any side effects. Those who do may have a follow-up visit. At this visit, they may have additional blood tests performed.
Participation will last from 8 to 12 weeks.
- Detailed Description
Sickle Cell Disease (SCD) is an inherited monogenic hemoglobin disorder caused by a mutation in the gene encoding the beta globin subunit of adult hemoglobin (HbA) resulting in a substitution of valine for glutamic acid at position 6 and thus producing hemoglobin S (HbS). When deoxygenated, HbS polymerizes, rendering the red cell rigid, viscous, and abnormally adherent to the capillary endothelium. This impedes blood flow in the microcirculation, causing ischemia and microinfarcts that lead to painful crises, cerebrovascular stroke, renal impairment, venous blood clots, retinopathy and other end-organ damage. The current scientific literature recognizes the contribution of an acquired hypercoagulable state in SCD to vascular pathobiology, chronic organ dysfunction, and mortality.
Like cancer, SCD is associated with a hypercoagulable state and patients have a high risk of new onset and recurrent venous thromboembolism (VTE). Elevated blood levels of the procoagulant protein tissue factor and its activator, protein disulfide isomerase (PDI) in patients with SCD suggest a causal role for these proteins in the development of venous blood clots. In cancer patients, inhibiting plasma PDI activity with isoquercetin (IQ) led to a significant reduction in VTE biomarkers (soluble P-selectin and D-dimer) and venous thrombosis over the short term. These findings provide support to test the hypothesis that isoquercetin treatment in sickle cell disease would diminish thrombo-inflammatory biomarkers and attenuate the hypercoagulable state.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Participants with Sickle Cell Disease Receiving Placebo Placebo Placebo once daily, by mouth for 28 days in participants with Sickle Cell Disease. Participants with Sickle Cell Disease Receiving Isoquercetin Isoquercetin Isoquercetin 1000 mg, once daily by mouth for 28 days in participants with Sickle Cell Disease.
- Primary Outcome Measures
Name Time Method Mean Change in the Plasma Soluble P-selectin Level Baseline and Day 28 Mean change in plasma soluble P-selectin level comparing the baseline versus IQ or placebo.
- Secondary Outcome Measures
Name Time Method Number of Participants That Tolerated Study Drug Up to day 28 Number of participants that tolerated study drug for full duration of study
Mean Change in Vascular Cell Adhesion Molecule Baseline and Day 28 Mean Change in Vascular Cell Adhesion Molecule (inflammation marker) comparing baseline to Day 28
Mean Change in D-Dimer Baseline and Day 28 Mean Change in D-Dimer comparing baseline and end of study
Mean Change in Plasma Protein Disulfide Isomerase Activity Baseline and 28 days Mean Change in Plasma Protein Disulfide Isomerase Activity comparing baseline and end of study
Median Change of Tissue Factor Vesicle Number Baseline and Day 28 Median change of Tissue Factor Vesicle Number comparing baseline and end of study
Mean Change in Tissue Factor Vesicle Procoagulant Activity Baseline and Day 28 Mean change in tissue factor vesicle procoagulant activity comparing baseline and end of study
Median Relative Blood Flow Index (rBFI) Determined by Near-infrared Spectroscopy (NIRS) Day 28 Median Relative Blood Flow Index (rBFI) determined by Near-infrared spectroscopy (NIRS).
Near-infrared spectroscopy (NIRS) is a noninvasive technology that measures blood flow by directing near-infrared light into tissue, collects scattered light due to red blood cell movements using photodiodes, and calculates the blood flow index (BFI) using the correlation diffusion equation (CDE). Briefly, participants were seated upright and NIRS probe and a blood pressure cuff was placed on the right arm and resting baseline data was collected for three minutes followed by occlusion of the blood flow for three minutes and reperfusion recorded for three minutes. The post-occlusion hyperemic reperfusion response represented as the relative Blood Flow Index (rBFI) is determined by normalizing the maximal change in light absorption following occlusion (dBFI) by the corresponding time interval (dt); (rBFI = dBFI/dt; unit (cm\^2/s)/s)\].Mean Percent Adherence to Study Drug Baseline and Day 28 Mean percent adherence to study drug. Adherence was defined as number of study drug pills participant took divided by number of study drug pills dispensed multiplied by 100.
Number of Adverse Events Grade 2 and Above Up to Day 56 Number of adverse events Grade 2 and above using Common Terminology Criteria for Adverse Events (CTCAE) 5.0
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States